This application requests continuing Medical Scientist Training Program (MSTP) support for the Combined MD/PhD Training Program at the University of Minnesota. Originally funded in 1988, the Program remains committed to a single goal: to train physician-scientists equipped to push technology and clinical application to a level of investigative excellence that will have a direct impact on the diagnosis and treatment of human disease. The MSTP provides instruction leading to the MD and PhD degrees in approximately 8 years, although curriculum changes make completion in 7 years a feasible goal. The Program employs a sequential training sequence of medical school (2 years) >graduate school (3-4 years) >medical school (1.5 years). Students conduct a minimum of 3 laboratory rotations during their initial 18 months in the Program, and can choose from over 100 preceptors with research opportunities that span the gamut of disciplines in contemporary biomedical research, as well as biomedical engineering and epidemiology. Future research opportunities will be enhanced by a major expansion of laboratory facilities, including the construction of 4 new research buildings in the East Gateway Biomedical Discovery District at the University of Minnesota. Multiple requirements/opportunities facilitate the essential goal of integrating fundamental scientific training with the development of competent and compassionate physicians. A centerpiece of this integration is a course ("Ambulatory Clinics for the Physician Scientist") in which students conduct clinical rotations with the physician-scientist of their choosing. Taken in the final year of graduate training, the course promotes thinking at a scientific/patient care boundary and refreshes students'clinical skills. Program leadership consists of a Director, Associate Director, and a Steering Committee made up of faculty from basic science and clinical departments. The Program recruits from a pool of gifted national applicants who can present a compelling case for a dual interest in science and medicine. The past 5 years have witnessed the complete elimination of any attrition problems, an enhanced curriculum that integrates scientific and clinical training, scientific accomplishments published in premiere journals (eg, Science and Nature), and residency choices that continue to promote academic career development. As of July 2009 there are 56 students in the Program (40% women, 14% under-represented minorities) from colleges and universities throughout the United States. These students are blessed with talent, highly productive (9 have individual F30 awards), and totally committed to a career in biomedical research. Our goal for the next 5 years is to continue our upward trajectory and witness the successful integration of our students into the fabric of biomedical research.